Lupus anticoagulant (LA) is a circulating anticoagulant that has been reported for the first time in SLE (Systemic Lupus Erythematosus) patients. In the case of LA-positive patients, from a clinical standpoint, bleeding diathesis is barely recognized, and the patients rather exhibit thrombotic diathesis. However, in the case of samples derived from LA-positive patients, a tendency of prolongation of the activated partial thromboplastin time (APTT) or the prothrombin time (PT) is exhibited in vitro. From the research that followed, it was made clear that LA is an autoantibody to complexes of phospholipids having negative charges and proteins in blood such as β2-glycoprotein I (β2GPI) or prothrombin, and currently it is known that LA is detected in large quantities even in diseases other than SLE. Particularly, the frequency of occurrence is high in the pathologic conditions of diseases that are generically referred to as “antiphospholipid syndrome (APS)”, and LA is considered as one of the laboratory findings in connection with the diagnostic criteria for the diseases (Non-Patent Document 1).
LA is defined as an immunoglobulin which inhibits phospholipid-dependent coagulation reactions in vitro (APTT, kaolin clotting time, dilute Russell's viper venom time, and the like), without inhibiting the individual coagulation factor activities, and LA is not a single antibody. For example, as some examples of antibodies responsible for LA, anti-cardiolipin-β2GPI complex antibody, anti-phosphatidylserine-prothrombin complex antibody and the like have been found, and there are measurement systems based on the ELISA method. However, the existence of antibodies responsible for LA other than these is not denied, and even if all of these already known responsible antibodies are negative, there still are cases in which LA becomes positive.
As the reagents for LA detection, reagents for blood coagulation time measurement containing phospholipids are generally used. When LA is contained in a specimen, LA binds with phospholipids in the reagent. Therefore, phospholipids required to advance the coagulation reaction in vitro become insufficient, and the blood coagulation time is prolonged. Accordingly, LA positivity can be determined based on the prolongation of the blood coagulation time. Examples of the reagents for LA detection include reagents for APTT, PT, and dilute Russell's viper venom time (dRVVT).
Furthermore, a blood coagulation correction test (hereinafter, also referred to as “blending test” or “mixing test”) in which a reagent for blood coagulation time measurement containing phospholipids is used, normal plasma is added to a test plasma, and the extent of the blood coagulation time of the test plasma being corrected (normalized) is plotted to determine the cause, has also been carried out (Non-Patent Document 2).
As a commercially available reagent for LA detection, a reagent for dRVVT-based analysis called LA test “GRADIPORE” (manufactured by Medical & Biological Laboratories Co., Ltd.) is used. With this reagent, the presence or absence of LA in a specimen is determined on the basis of the ratio of the coagulation time taken by addition of Russell's viper venom and the coagulation time taken by addition of Russell's viper venom and an excessive concentration of phospholipids.
Furthermore, in addition to the reagent described above, a reagent for LA detection called STACLOT LA (manufactured by Diagnostica Stago, Inc.) is also commercially available. With this reagent, the presence or absence of LA in a specimen is determined by examining the difference in the coagulation time for APTT between a sample obtained by adding normal plasma and excess phospholipids to the test plasma, and a sample obtained by adding only normal plasma to the test plasma.
However, in the existing methods described above, it is difficult to discriminate whether the cause of prolongation of the coagulation time lies simply in the deficiency of coagulation factors, in the inhibitors of the coagulation factors, or in LA, only by measuring a single item using each of the reagents. On the other hand, since the therapeutic strategy may vary depending on the difference in the cause, discrimination thereof is important. Therefore, these LA detection methods are rarely used singly, and it is recommended to combine two or more kinds of examinations and comprehensively determine the results (Non-Patent Document 3).